SREs

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Cultured reticulocytes can supplement transfusion needs and offer promise for drug delivery and immune tolerization. They can be produced from induced pluripotent stem cells (iPSCs), but the 45-day culture time and cytokine costs make large-scale production prohibitive. To overcome these limitations, we have generated IPSCs that express constitutive SCF receptor and jak2 adaptor alleles. We show that iPSC lines carrying these alleles can differentiate into self-renewing erythroblast (SRE) that can proliferate for up to 70 cell-doubling in a cost-effective, chemically-defined, albumin- and cytokine-free medium...

INTRODUCTION: Breast cancer-related bone metastasis can lead to skeletal-related events (SREs), which decrease patient quality of life. Inhibition of osteoclastogenesis is a key treatment for SREs; however, the availability of clinical drugs remains limited, and all existing ones disrupt physiological bone formation, while exhibiting no effect on patient survival time. OBJECTIVES: This study aimed to identify a novel osteoclast inhibitor for the treatment of breast cancer-induced SREs...

There are limited data regarding the impact of disease-related complications on the survival of multiple myeloma (MM) patients. The primary objective of this study was to determine the prevalence of disease-related complications, including hypercalcemia, renal insufficiency, anemia, and bone lytic lesions in MM patients. The secondary objectives were to determine clinical characteristics, treatment outcomes, and the association of disease-related complications and mortality. A retrospective chart review of MM patients from November 2014 to December 2019 was conducted...

INTRODUCTION: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC. METHODS: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850)...

BACKGROUND: Bone metastasis in advanced cancer is challenging because of pain, functional issues, and reduced life expectancy. Treatment planning is complex, with consideration of factors such as location, symptoms, and prognosis. Prognostic models help guide treatment choices, with Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) showing promise in predicting survival for initial spinal metastases and extremity metastases treated with surgery or radiotherapy. Improved therapies extend patient lifespans, increasing the risk of subsequent skeletal-related events (SREs)...

IMPORTANCE: The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear. OBJECTIVE: To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed...

STUDY DESIGN: Predictive study utilized retrospectively collected data. OBJECTIVE: The primary objective was to evaluate the predictive association between the Spine Instability Neoplastic Score (SINS) and Skeletal-related events (SREs). Secondary objectives included examining characteristics of cases with SINS < 6 among those who developed SRE, and evaluating the impact of additional predictors on prediction accuracy. SUMMARY OF BACKGROUND DATA: Advances in cancer treatment have prolonged the lives of cancer patients, emphasizing the importance of maintaining quality of life...

PURPOSE: We report a 10-year experience in cancer therapy with concomitant treatment of percutaneous thermal ablation (PTA) and immune checkpoint blockers (ICBs). MATERIAL AND METHODS: This retrospective cohort study included all patients at a single tertiary cancer center who had received ICBs at most 90 days before, or 30 days after, PTA. Feasibility and safety were assessed as the primary outcomes. The procedure-related complications and immune-related adverse events (irAEs) were categorized according to the Common Terminology Criteria for Adverse Events v5...

BACKGROUND: Skeletal-related events (SREs), including the pathological fracture, surgical treatment or radiation of bone lesions, malignant spinal cord compression, hypercalcemia, are important considerations when managing metastatic bone tumors; however, owing to their rarity, the incidence of SREs in patients with Ewing sarcoma remains unknown. METHODS: We retrospectively reviewed the clinical data from 146 patients with Ewing sarcoma treated at a single institution from 2005 to 2019...

PURPOSE: Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India. MATERIALS AND METHODS: A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks)...

Dielectric elastomer generator (DEG), which consists of a dielectric elastomer (DE) film sandwiched between two flexible electrodes (FEs), has the advantages of lightweight, high energy density, and high energy conversion efficiency, providing a simple and feasible solution for harvesting energy from human motion or nature. As crucial constituents of DEG, FEs are expected to possess excellent conductivity and compliance. Nevertheless, there is currently no quantitative characterization method for FE compliance...

The limited proliferative capacity of erythroid precursors is a major obstacle to generate sufficient numbers of in vitro-derived red blood cells (RBC) for clinical purposes. We and others have determined that BMI1, a member of the polycomb repressive complex 1 (PRC1), is both necessary and sufficient to drive extensive proliferation of self-renewing erythroblasts (SREs). However, the mechanisms of BMI1 action remain poorly understood. BMI1 overexpression led to 10 billion-fold increase BMI1-induced (i)SRE self-renewal...

Splicing is controlled by a large set of regulatory elements (SREs) including splicing enhancers and silencers, which are involved in exon recognition. Variants at these motifs may dysregulate splicing and trigger loss-of-function transcripts associated with disease. Our goal here was to study the alternatively spliced exons 8 and 10 of the breast cancer susceptibility gene CHEK2. For this purpose, we used a previously published minigene with exons 6-10 that produced the expected minigene full-length transcript and replicated the naturally occurring events of exon 8 [Δ(E8)] and exon 10 [Δ(E10)] skipping...

It is now widely accepted that aberrant splicing of constitutive exons is often caused by mutations affecting cis-acting splicing regulatory elements (SREs), but there is a misconception that all exons have an equal dependency on SREs and thus a similar vulnerability to aberrant splicing. We demonstrate that some exons are more likely to be affected by exonic splicing mutations (ESMs) due to an inherent vulnerability, which is context dependent and influenced by the strength of exon definition. We have developed VulExMap, a tool which is based on empirical data that can designate whether a constitutive exon is vulnerable...

Spatial recharge estimation uncertainty is directly proportional to uncertainty in input precipitation data Thus, the main objective of this study was to investigate the recharge uncertainty by using improved spatial rainfall observations. The physically based fully distributed hydrological model WetSpa was used to simulate 20,000 possible combinations of parameters for two model setup. The M1 model setup was developed based on the rainfall measurements obtained from rain gauge stations scattered in and around the Tikur-Wuha watershed in Ethiopia, while M2 model setup was developed using bias-corrected satellite rainfall estimates (SREs) based on Climate Hazards Group InfraRed Precipitation (CHIRP) merged with relevant ground station records...

Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover markers (BTM) with dual-energy X-ray absorptiometry (DXA) assessment could identify early BM progression and risk of skeletal-related events (SREs) during zoledronate treatment. Before the initiation of zoledronate (T0) and after six months of treatment (T1), serum levels of five BTM were measured, and patients (N = 47) underwent DXA evaluation...

In analysis of complex samples, the stability and sensitivity of surface-enhanced Raman scattering (SERS) substrates may be compromised by matrix interference. To address this issue, a membrane substrate was prepared for fast enrichment, separation, and detection of chrysoidine all-in-one. The silver nanoparticles modified sulfur-containing POSS polymer (AgNPs/POSS-P-S) SERS membrane substrate was fabricated using polyhedral oligomeric silsesquioxane (POSS) as support materials. Through in-situ growth, AgNPs were uniformly modified on POSS-P-S to ensure the stability and SERS activity of the membrane substrate...

BACKGROUND: Early palliative/pre-emptive intervention improves clinical outcomes and quality of life for patients with metastatic cancer. A previous signal-seeking randomized controlled trial (RCT) demonstrated that early upfront radiotherapy to asymptomatic or minimally symptomatic high-risk osseous metastases led to reduction in skeletal-related events (SREs), a benefit driven primarily by subgroup of high-risk spine metastasis. The current RCT aims to determine whether early palliative/pre-emptive radiotherapy in patients with high-risk, asymptomatic or minimally symptomatic spine metastases will lead to fewer SREs within 1 year...

BACKGROUND: Breast cancer is the most common cancer in women and most often metastasizes to the bone, resulting in skeletal-related events (SREs). Bone-modifying agents (BMAs) including denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b ligand (RANKL), and pamidronate, a bisphosphonate, are used to prevent these adverse events. METHODS: To analyze the efficacy of denosumab versus pamidronate, we used the TriNetX research platform and compared the outcomes of pathologic fracture, spinal cord compression, and overall 5-year survival rate between each pharmacotherapy...